The goal of the project described in this application is to define the receptor systems controlling the recognition of MHC I by rat NK cells. Functional studies show that rat NK cells must express MHC-binding receptors inhibits (allo-inhibition) or activates (allo-activation) natural killing. T identify these receptors, the investigators have localized the genes controlling NK cell alloresponses near or within the Ly-49 locus of lectin-like receptors on rat chromosome 4. They have shown that NK cells form rats that are defective in alloactivation are also deficient in Ly-49 expression. They have cloned and sequenced 5 members of the rat Ly-49 family and have raised mAbs reactive against 2 Ly-49 proteins. They have also produced new mAbs against receptors implicated in NK cell alloresponses, and they have cloned these receptor cDNAs. One receptor (STOK1/2) is a novel L-49 molecule, and the others comprise a previously undescribed family of NK lectins, which they have termed STOK9.Their objective is to show that the Ly-49 and STOK9 receptors control NK cell allo-inhibition and allo-activation in rats. Toward this end they have 5 specific aims. 1] Expand the panel of Ly-49 antibodies for use in Ly-49 functional studies. 2] Using blocking or stimulating anti-Ly-49 mAbs, they will examine the MHC specificities of each Ly-49 on rat NK cells and on Ly-49-transfected RNK-16 cell lines. 3] They will clone cDNAs encoding new members of the STOK9 family. 4] They will produce mAbs specific for newly cloned STOK9 proteins. 5] As in Aim 2, they will use these reagents to examine the MHC specificities of STOK9 receptors on rat NK cells and on STOK9-transfected RNK-16 cell lines.